The gut-brain axis in diabetic neuropathy, cognitive impairment, and emotional disorders

Abstract

Diabetes mellitus has become a global public health challenge, with a steadily rising prevalence that imposes substantial socioeconomic burdens. Over recent years, the gut-brain axis (GBA) has garnered significant attention as a crucial biological framework. GBA denotes the intricate network of bidirectional signaling between the gut and the brain via neuronal, endocrine, and immunological pathways, with the connections among gut bacteria, gut barrier function, and neuroendocrine factors significantly influencing the progression of diabetes mellitus. Studies indicate that disruptions in gut microbiota balance and compromised intestinal barrier integrity are significantly associated with the onset of insulin resistance and diabetes mellitus. Gut flora regulates energy metabolism, insulin sensitivity, and immune responses via the generation of metabolites (e.g., short-chain fatty acids), while impaired gut barrier function can trigger systemic chronic inflammation, which in turn promotes insulin resistance. The GBA also influences appetite, energy balance and insulin secretion through neuroendocrine pathways. Imbalances in the gut microbiota may lead to neuroendocrine dysregulation, thereby accelerating diabetes pathogenesis. New diabetes treatment strategies are being explored based on research on the GBA. Modulation of the intestinal microbiome, restoration of gut barrier integrity, and correction of neuroendocrine dysregulation may offer novel avenues for managing diabetes and its associated complications. In conclusion, revealing the multidimensional pathogenesis of diabetes mellitus from the perspective of the GBA will help to develop more effective therapeutic strategies.